Results of this study showed that although nocturnal application of NIV is associated with faster reduction in the PaCO2 levels, higher PS requirement and prior home ventilation usage are predictors for late and poorer response to NIV in AHcRF.
In this study, although there were no significant differences in the total durations of daily NIV application of nonresponsive and responsive groups, significantly higher percentage of patients in the responsive group received NNIV than the nonresponsive group. These results suggest that nocturnal usage of NIV may have an additional effect or benefit on PaCO2 control independently from the total daily usage time even during acute exacerbations.
Studies have shown that patients with neuromuscular disease (NMD), severe kyphoscoliosis, COPD, and OHSs are at risk for nocturnal hypoventilation and they are frequently good responsive to nocturnal ventilation.[15
] Probably, because of this reason, all night long use of NIV was an independent predictor for NIV response in the first 24 hours in our study group.
A mild CO2
retention normally occurs with the onset of sleep and increases further during the rapid eye movement (REM) sleep. Respiratory muscle weakness as seen in NMDs or increased work of breathing as seen in obese and COPD patients exacerbates this normally occurring mild CO2
] The mechanical disadvantages caused by severe COPD predispose to ventilatory hyporesponsiveness to CO2
and nocturnal hypoventilation, especially during REM sleep. This further blunts central drive, promotes more CO2
retention. Ballard et al
. showed that upper airway resistance rises by 164% and 263% and VT falls by 20% and 35% during non-REM and REM sleep, respectively.[19
] The evidence suggests that at least for restrictive thoracic disorders and COPD, NNIV acts mainly by ameliorating nocturnal hypoventilation, stabilizing gas exchange, and enhancing CO2
In our study, mean BMI is higher than 30 kg/m2
in both groups, nearly 40% of the patients had sleep- or obesity-related hypoventilation syndromes and more than 50% of the patients had COPD. OHS is the combination of hypercapnia and obesity (body mass index≥30 kg/m2
). Approximately 80 to 90% of OHS patients have underlying OSAS and mechanisms of action of NNIV in these patients include reducing the respiratory load, increasing minute volume for a given breathing effort, and providing ventilation during central apneic events (if a backup rate is used).[20
] A prospective cohort study about OHS patients revealed that low ventilatory responsiveness to CO2
was associated with more hypoventilation during REM sleep and greater daytime sleepiness, abnormalities that were ameliorated by short-term therapy with NNIV.[22
Another finding of the study is that patients using home mechanical ventilation or in other words with chronic hypercapnia were significantly associated with slower and lower response rates to NIV therapy in the ICU during acute attacks. This result is very important because in recent years, the number of patients with chronic respiratory failure using home mechanical ventilation is progressively increasing.[7
] We do not have national data showing home mechanical ventilation usage rates, but at least our previous studies (16% and 21%) and this study (31%) revealed that these patients are also increasing with years in our country probably due to increasing smoking and obesity rates.[12
] Studies performed with stable chronic hypercapnic patients and investigating the effect of home mechanical ventilation on PaCO2
levels show that even under this therapy, PaCO2
levels of the patients are around 55 to 60 mmHg.[24
] Probably for this reason, we could not decrease PaCO2
level below 50 mmHg, particularly in group 1. Supporting these findings of our study, group 1 was discharged as more hypercapnic than group 2 also. It is impossible to know or guess the baseline PaCO2
levels of the patients during admission to emergency department in patients with AHcRF. But, if the information of home ventilation usage can be obtained, then the intensivist can predict that hypercapnia is chronic and can be resistant.
Results of this study showed that to increase PS levels may not be the only and the best solution to decrease PaCO2
levels and if the patient does not respond to higher inspiratory pressures, intensivist should consider other choices. In our study, we could not achieve to reduce PaCO2
below 50 mmHg level, despite we use higher level of PS in group 1. According to protocol of our study, we targeted a VT between 450 and 500 ml considering the body weights of patients and increase PS levels to reach this target VT. Results showed that mean VT of the both groups is around 500 ml and group 1 required significantly higher levels of PS. But still, reduction in the PaCO2
level was lower in group 1 than in group 2. A possible explanation of this result is the increase in air leakage by increasing the PS level and worsening patient ventilator synchrony. Studies performed in mechanically ventilated patients have shown that higher PS levels may cause ineffective triggering and cycling off asynchronies. In a study where assistance was varied between 0% and 100%, Leung et al
. found that there were almost no ineffective efforts below 60% of assistance, but ineffective efforts increased gradually when assistance was 60 to 100%.[29
] In a cohort of 62 intubated patients, Thille et al
. recently found that ineffective triggering represented almost 90% of all asynchronies during PS ventilation (PSV) and COPD was a risk factor for asynchrony. Patients with ineffective triggering had a higher VT and higher PS.[30
] This asynchrony has been described with different diseases but is observed mainly in patients with expiratory flow limitation leading to the development of intrinsic PEEP.[27
] Another asynchrony caused by higher levels of PS and seen frequently during NIV due to leaks is prolonged inspiration as part of a cycling of asynchrony.[31
There are some important limitations of this study. First of all, it is a retrospective study, so we could not assess some important parameters like amount of leak or asynchronies. But we believe that it was a good representative of current status about the use of NIV therapy in acute hypercapnic patients in ICU. Secondly, this study was made with a heterogeneous group of the patients. Since we had a few number of patients with NMD, kyphoscoliosis, and postextubation respiratory failure, we could not evaluate separately the differences in the NIV response in these patients. A future prospective study with selected patient groups evaluating more parameters during NIV would be more effective in clarifying other factors associated with the NIV response in the first day of AHcRF.